- Adiponectin, Insulin Sensitivity, β-Cell Function, and Racial/Ethnic Disparity in Treatment Failure Rates in TODAY. [Journal Article]
- DCDiabetes Care 2017; 40(1):85-93
- CONCLUSIONS: HMWA is a reliable biomarker of treatment response in youth with type 2 diabetes. The diminutive treatment-associated increase in HMWA in NHB (∼50% lower) compared with NHW and H may explain the observed racial/ethnic disparity with higher therapeutic failure rates in NHB in TODAY.
- Weight change in the management of youth-onset type 2 diabetes: the TODAY clinical trial experience. [Randomized Controlled Trial]
- POPediatr Obes 2017; 12(4):337-345
- CONCLUSIONS: Although adjunctive intensive lifestyle intervention did not improve weight-related outcomes, weight changes in the full TODAY sample were associated with small, but significant improvements in cardiometabolic status, highlighting the importance of optimizing weight management in youth with T2DM.
- METFORMIN-SUSTAINED WEIGHT LOSS AND REDUCED ANDROID FAT TISSUE AT 12 MONTHS IN EMPOWIR (ENHANCE THE METABOLIC PROFILE OF WOMEN WITH INSULIN RESISTANCE): A DOUBLE BLIND, PLACEBO-CONTROLLED, RANDOMIZED TRIAL OF NORMOGLYCEMIC WOMEN WITH MIDLIFE WEIGHT GAIN. [Randomized Controlled Trial]
- EPEndocr Pract 2016; 22(5):575-86
- CONCLUSIONS: In combination with a novel carbohydrate modified diet, metformin enhanced 12-month weight loss and improved body composition in ethnically diverse normoglycemic, hyperinsulinemic women with midlife weight gain. These findings suggest that EMPOWIR's easily implemented dietary interventions, alone and in combination with pharmacotherapies that target hyperinsulinemia, merit additional investigation in larger, long-term studies.
- Efficacy and safety of avandamet or uptitrated metformin treatment in patients with type 2 diabetes inadequately controlled with metformin alone: a multicenter, randomized, controlled trial. [Randomized Controlled Trial]
- CMChin Med J (Engl) 2015 May 20; 128(10):1279-87
- CONCLUSIONS: Compared with uptitrated metformin, Avandamet treatment provided significant improvements in key parameters of glycemic control and was generally well tolerated.
- Correlated increase of omentin-1 and adiponectin by exenatide, avandamet and dietary change in diet-induced obese rats. [Journal Article]
- FBFolia Biol (Praha) 2013; 59(6):217-24
- Adipokines omentin-1 and adiponectin have been reported to improve insulin resistance. It is known that insulin sensitizers exenatide, avandamet, or diet change from high-fat to normal chow ameliorat...
Adipokines omentin-1 and adiponectin have been reported to improve insulin resistance. It is known that insulin sensitizers exenatide, avandamet, or diet change from high-fat to normal chow ameliorate metabolic disorders. However, whether these treatments increase omentin-1 levels in high fat-diet animals and the relationship between omentin- 1 and adiponectin remain largely unknown. We investigated the effect of insulin sensitizers exenatide and avandamet, and of dietary change on these adipokine levels, body weight, and insulin sensitivity in diet-induced obese rats. Obesity was induced in rats by high-fat diet feeding for 8 weeks, and then the rats were given exenatide, avandamet and diet change to normal chow, respectively, for additional 8 weeks. Compared to the high-fat control group, exenatide and avandamet treatment significantly induced adipose gene expression and elevated the circulation levels of omentin-1 and adiponectin, whereas they decreased the leptin gene expression and circulation level, which is associated with improvement of systemic insulin sensitivity and the glucose and lipid profile. Notably, there was a significant positive correlation between omentin-1 and adiponectin in the above regimens, suggesting that omentin-1 and adiponectin may contribute to the insulin-sensitizing effect of exenatide and avandamet.
- Impact of sex on the heart's metabolic and functional responses to diabetic therapies. [Randomized Controlled Trial]
- AJAm J Physiol Heart Circ Physiol 2013 Dec 1; 305(11):H1584-91
- Increased myocardial lipid delivery is a determinant of myocardial substrate metabolism and function in animal models of type 2 diabetes (T2DM). Sex also has major effects on myocardial metabolism in...
Increased myocardial lipid delivery is a determinant of myocardial substrate metabolism and function in animal models of type 2 diabetes (T2DM). Sex also has major effects on myocardial metabolism in the human heart. Our aims were to determine whether 1) sex affects the myocardial metabolic response to lipid lowering in T2DM, 2) altering lipid [fatty acid (FA) or triglyceride] delivery to the heart would lower the elevated myocardial lipid metabolism associated with T2DM, and 3) decreasing lipid delivery improves diastolic dysfunction in T2DM. To this end, we studied 78 T2DM patients (43 women) with positron emission tomography, echocardiography, and whole body tracer studies before and 3 mo after randomization to metformin (MET), metformin + rosiglitazone (ROSI), or metformin + Lovaza (LOV). No treatment main effects were found for myocardial substrate metabolism, partly because men and women often had different responses to a given treatment. In men, MET decreased FA clearance, which was linked to increased plasma FA levels, myocardial FA utilization and oxidation, and lower myocardial glucose utilization. In women, ROSI increased FA clearance, thereby decreasing plasma FA levels and myocardial FA utilization. Although LOV did not change triglyceride levels, it improved diastolic function, particularly in men. Group and sex also interacted in determining myocardial glucose uptake. Thus, in T2DM, different therapeutic regimens impact myocardial metabolism and diastolic function in a sex-specific manner. This suggests that sex should be taken into account when designing a patient's diabetes treatment.
- Development and validation of spectrophotometric and HPTLC methods for simultaneous determination of rosiglitazone maleate and metformin hydrochloride in the presence of interfering matrix excipients. [Journal Article]
- DDDrug Dev Ind Pharm 2014; 40(9):1190-8
- Two simple methods have been developed and validated for the simultaneous determination of rosiglitazone maleate (ROS) and metformin hydrochloride (MET) in synthetic mixtures and coated tablets in a ...
Two simple methods have been developed and validated for the simultaneous determination of rosiglitazone maleate (ROS) and metformin hydrochloride (MET) in synthetic mixtures and coated tablets in a ratio of 1:250 (ROS:MET). The first method was a spectrophotometric one. The minor component, ROS was determined by measuring the values of absorbance at λmax 312 nm and the D1 amplitudes at 331 nm where MET shows no absorption contribution. However, absorbance interferences from tablet excipients were successfully corrected by D1 at 331 nm zero-crossing technique. Study of spectral interference from tablet excipients was included in the text. Standard curves for Amax and D1 methods were in the concentration range 20.0-80.0 μg mL(-1). The major component, MET was determined both in binary mixtures and tablets by measuring its Amax at 236 nm. Extensive dilution eliminated any absorption contribution from the coexisting ROS or tablet matrix. Standard curves showed linearity in the concentration range 4.0-12.8 μg mL(-1). The second method was based on high performance thin layer chromatography (HPTLC) separation of the two drugs followed by densitometric measurements of their spots at 230 nm. The separation was carried out on Merck HPTLC aluminium sheets of silica gel 60 F254 using methanol:water:NH4Cl 1% w/v (5:4:1 v/v/v) as the mobile phase. Linear calibration graphs of peak area values were obtained versus concentrations in the range of 0.4-2.0 μg band(-1) and 20.0-100.0 μg band(-1) for ROS and MET, respectively. According to International Conference on Harmonisation (ICH) guidelines, different validation parameters were verified for the two methods and presented.
- Safety and tolerability of the treatment of youth-onset type 2 diabetes: the TODAY experience. [Randomized Controlled Trial]
- DCDiabetes Care 2013; 36(6):1765-71
- CONCLUSIONS: The TODAY study represents extensive experience managing type 2 diabetes in youth and found that the three treatment approaches were generally safe and well tolerated. Adding rosiglitazone to metformin may reduce GI side effects and hepatotoxicity.
- Effects of metformin, metformin plus rosiglitazone, and metformin plus lifestyle on insulin sensitivity and β-cell function in TODAY. [Randomized Controlled Trial]
- DCDiabetes Care 2013; 36(6):1749-57
- CONCLUSIONS: The beneficial change in insulin sensitivity and the resultant lower burden on β-cell function achieved in the first 6 months with metformin plus rosiglitazone appear to be responsible for its superior glycemic durability over metformin alone and metformin plus lifestyle. However, initial β-cell reserve and HbA1c at randomization are independent predictors of glycemic durability. Therefore, efforts to preserve β-cell function before significant loss occurs and to reduce HbA1c may be beneficial in the treatment of youth with type 2 diabetes.
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- Treatment effects on measures of body composition in the TODAY clinical trial. [Randomized Controlled Trial]
- DCDiabetes Care 2013; 36(6):1742-8
- CONCLUSIONS: Despite differential effects on measures of adiposity (with M+R resulting in the most and M+L in the least fat accumulation), group differences generally were small and unrelated to treatment effects in sustaining glycemic control.